DESCRIPTION, OVERALL (provided by applicant): The Silvio O. Conte Digestive Disease Core Research Center at Tufts-New England Medical Center (called GRASP) supports basic research on digestive diseases. The interests of GRASP investigators include microbial pathogenesis, receptors and intracellular signaling, developmental and cell biology of the gastrointestinal tract, cancer, and obesity. GRASP has 51 independently funded members at Tufts-NEMC and Tufts Univ. School of Medicine. From 1998 to October 2003, GRASP members published close to 300 full-length, peer reviewed articles. The Center supports a pilot/feasibility project program that funded 28 innovative projects in digestive disease from 1998- 2003, many resulting in new extramural funding. GRASP program enrichment integrates the center with the scientific community at Tufts by sponsoring distinguished visiting scientists. An external scientific advisory committee comprised of highly respected scientists from around the country reviews the Center's activities annually. GRASP cores include Intestinal Microbiology (small and large scale microbial culture and protein purification), Imaging & Cell Analysis (confocal microscopy, laser microdissection, and histology), Gene Expression & Genomics (transgenic mice, real time PCR, microarrays, bioinformatics), Antibody & Cell Culture (production of monoclonal antibodies and adenoviruses), and Administration. In the past 2 years, eight new scientists became members, expanding our research base in pancreatitis, neuroscience, and cancer. Several cores are shared with other centers at Tufts to reduce duplication of effort and costs, and to promote scientific interaction. Plans for the next 5 years include incorporation of newer imaging techniques like spinning disk confocal microscopy for research on signaling pathways, application of gene expression profiling to small numbers of highly specialized cells by combining laser microdissection with microarrays, studies to utilize Drosophila as a model organism to study digestive function, and expansion of protein purification projects for microbial virulence proteins.